Thankfully the researchers from the STEP trials pulled this together so I don’t have to try and redneck fix a series of trials together to complete my own comparison! I’ll happily admit I did not get any of the handyman skills in our family. My little brother definitely was given all of that genetic material. The kid could take your entire car apart and put it back together and it would likely run better than it did previously. I, on the other hand, could put windshield washer fluid in it and change a flat tire if I am in a pinch, but anything more and the car would likely blow up. Hence why I stick to telling bad jokes and making YouTube videos!
Soo… tell me about the recent STEP trial…
Anywho, the STEP 8 Trial is hot off the press, published in January 2022. The authors of this paper directly compared Saxenda 3mg daily and Wegovy 2.4mg once weekly. One thing that is exciting about this paper is that it is a superiority trial – the goal was to see which drug was superior to the other.
Most trials that compare two drugs head to head are usually done in what is called a non-inferiority trial. Where the goal is to say one drug is not inferior or worse than another drug, it is just as effective or better etc., which makes sense. If you are a drug company and you set out to do a trial and your drug looks worse than your competitor’s drug, that is not going to bode well for your future drug sales.
However, in this scenario, Novo Nordisk is the manufacturer of both Saxenda and Wegovy. So if one drug looks bad in comparison to the other, that is OK as they will simply sell more of the other drug. Further, Novo knew going into this trial that Wegovy was likely going to be more effective than Saxenda. And, with Saxenda coming off patent in the near future, generics will become more readily available, making Wegovy the shining star that they want to sell more of anyways. You know, business politics, etc.
It is no wonder Novo has not reached out to offer sponsorship for my videos!
Soo… tell me MORE about the recent STEP trial…
Rubino and friends recruited 338 individuals with a BMI of > 30 or a BMI > 27 with 1 weight-related comorbidity, such as diabetes, or high blood pressure, and split these individuals into 4 groups.
The first 2 groups were Wegovy titrated to a dose of 2.4mg once weekly vs. a matched placebo, and Saxenda titrated to a dose of 3mg daily vs. matched placebo. This was done as Wegovy is once-weekly dosing and Saxenda is once-daily dosing; with no matched placebo groups, it would be very clear to participants which group was getting what drug and could certainly lead to some bias being introduced.
Humans are funny creatures – if they think they are receiving a more effective agent ie. Wegovy, they will likely try harder to lose weight than they might in the comparison group. Similarly, researchers may provide less intensive counselling etc. Funny bias-prone creatures we are! That is why we have the scientific process, to help mitigate our shortcomings as imperfect beings.
The four groups were then titrated to the appropriate dose of a given drug or placebo, and they were also provided counselling from a qualified healthcare professional every 4 to 6 weeks in order to adhere to a calorie deficit of 500 calories/day and obtain > 150 minutes of physical activity weekly. Participants were followed for a period of 68 weeks.
What did Rubino and friends find?
I think I have already let this cat out of the bag but Wegovy was obviously found to be more effective.
After 68 weeks, the individuals who were taking Wegovy were found to have lost 15.8% of their baseline body weight, whereas those taking Saxenda lost 6.4% of their baseline body weight.
For clarity, what a loss from baseline means, is if an individual starts at 100kg and loses 15.8%, they would have lost 15.8kg or 34.8lbs with Wegovy and 6.4kg or 14.1lbs with Saxenda.
Obviously, this is a significant amount of weight loss for both groups, but certainly more so with Wegovy. Further, these are similar results to what we have seen in other trials which is always a nice confirmation that the researchers completed a study appropriately.
Were there any side effects?
There were some interesting adverse events.
As expected Wegovy led to slightly more GI disorders (84.1% vs. 82.7%) such as nausea, constipation, diarrhea, and vomiting. There were more individuals that stopped Saxenda due to GI side effects compared to Wegovy – 6.3% vs. 0.8%. This makes me think there may have been some level of potential bias – especially looking at the supplementary material.
There was a larger number of people, 14% vs. 3%, in the Wegovy vs. Saxenda group that did not reach the top target dose of 2.4mg once weekly and 3mg once daily respectively. The study did allow for people in the Wegovy group to stay at 1.7mg once weekly if they did not tolerate the 2.4mg once weekly dose and there was not a similar caveat for the Saxenda group. This may mean people were pushed, or I should say encouraged, more assertively to get up to the top dose of Saxenda vs. Wegovy, which if you are not tolerating a said medication, may lead to more side effects and for you to ultimately say GTFO.
These results don’t necessarily add up to what I see in practice and given that Novo Nordisk sponsored the trial and oversight over the entire thing, we can’t rule out the fact they may have made a few tweaks to make Wegovy look as good as possible; great outcomes and fewer side effects?! Say what?! I mean, money does really talk and Novo has a responsibility as a corporation to its shareholders and not necessarily to you, the consumer.
Fack I am clearly feeling a tad petty today!
Final Thoughts from Dr. Dan
To wrap things up, Rubino and friends did show that Wegovy, as expected, is significantly better than Saxenda in weight-loss management. While the side effects were similar between both treatment groups in clinical experience and from other trial data, I would argue Wegovy leads to more adverse effects, simply because it is more potent. Again, this is something we might expect.
Does this mean it won’t work for you? No, not at all. You might just need a lower dose or do a slower dose titration in order to ensure the medication is tolerable and effective, for you!
As always, speak with and follow up with your care team to ensure this treatment is right for you!
Until next time you beautiful people! Always remember small tweaks lead to massive peaks.
-Dr. Dan
References
Rubino DM, Greenway FL, Khalid U, et al. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults with Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial. JAMA – Journal of the American Medical Association. 2022;327(2):138-150. doi:10.1001/JAMA.2021.23619
